A computational model of dopamine neuron
College of Charleston
Midbrain dopamine neurons are involved in motivation and the control of movement, and have been implicated in various pathophysiologies such as Parkinson's, schizophrenia, and drug abuse. We focused on modeling the basis for pacemaker firing, and mechanisms are proposed for transition to burst firing in vitro, with the goal of extrapolating these insights to the situation in vivo. A minimal, single-compartment Hodgkin-Huxley (HH)-type parallel conductance membrane model was constructed in order to capture the essential mechanisms underlying the SOP and square wave oscillations. Our model retains a fundamental role for well-known L-type current in the depolarizing phase of the slow oscillatory potential, possibly aided to varying degrees by other calcium currents. In addition, we hypothesized that the plateau potentials repolarization was determined by a slowly activating potassium current, tentatively identified as an ERG (ether-a-go-go-related) potassium channel. Numerical results are in good agreement with experimental measurements. Based on our numerical simulations, we hypothesize that the ERG current helps to relieve depolarization block, and may relieve it in vivo as well. A role for depolarization block of midbrain dopamine neurons has been postulated in the treatment of schizophrenia with anti psychotic drugs. Some antipsychotic drugs have the side effect of blocking ERG channels, including the cardiac. The blockade of the cardiac ERG channel may be responsible for some instances of cardiac arrhythmias and sudden death. We showed that the ERG current likely contributes to relief from depolarization block in a nonphysiological setting, under conditions of apamin-induced block of the SK channel in a slice preparation.
Last Modified: Jan 18, 2006
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